Low-Cal Diet Keeps Aging Rats Active

by John Gever John Gever,Deputy Managing Editor, MedPage Today
November 12, 2013

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Note that these studies were published as abstracts and presented at a conference. These data and conclusions should be considered to be preliminary until published in a peer-reviewed journal.

SAN DIEGO -- A diet with 30% fewer calories than normal preserved the interest and ability in laboratory rats to move around as they aged -- an effect also seen with exercise, researchers said here.

Among 1-year-old rats with relatively high activity levels at baseline, almost no reduction was seen over the next 18-24 weeks when kept on the low-calorie diet, whereas rats allowed to feed freely showed an approximately 25% reduction in activity (P<0.05), said Michael Salvatore, PhD, at Louisiana State University's campus in Shreveport.

Also, rats that were relatively sedentary at baseline showed significant increases in activity over the following 18 weeks when put on the low-cal diet, Salvatore said at the Society for Neuroscience's annual meeting. The sedentary rats initially showed no change in activity and then had significant declines, so that when they reached the 24-week mark, their activity levels had fallen by 20% from their already low baseline.

In interpreting what the findings might mean for humans as they age, Salvatore cautioned that a 30% reduction in calories is probably not practical. Future studies should examine whether a smaller reduction, like 15%, still produces benefits and also whether caloric restriction preserves activity when the diet is initiated at an older age, he said.

Another researcher in Salvatore's lab, Jennifer Arnold, led a separate study reported here that showed 12 days of forced treadmill exercise in aged rats increased their spontaneous activity relative to nonexercised control animals.

Both studies were intended to address the problem of bradykinesia in elderly humans, the general slowdown in their physical activity. It's a prominent feature of Parkinson's disease but is also frequently seen in other older individuals regarded as neurologically normal.

Arnold's study suggested that the effect of exercise is not merely to improve cardiorespiratory or musculoskeletal function. In her rat model, it boosted dopamine levels in the substantia nigra, which may reflect or even prompt a psychological interest in physical activity.

Salvatore said his lab is now actively investigating the effects of caloric restriction as well as exercise in the entire nigrostriatal dopamine neuronal system.

In the diet study, Salvatore and colleagues used F1 hybrid animals obtained by crossing Fischer 344 rats with ordinary Norway brown rats. These rats are popular for aging studies because they have long lifespans and their physical function declines slowly.

Their colony was raised normally up to 12 months of age, then assigned either to the 30% caloric reduction or to ad libitum feeding. The animals' activity levels were measured every 6 weeks for 24 weeks, using open-field boxes equipped with sensors to track the rats' distance covered, time spent in motion, and their speed.

At the first baseline measurement, the median activity level was calculated with those above it classified as having high baseline activity (the "Bruce Jenners," Salvatore quipped) and those below as having low activity.

Across both groups, those assigned to unlimited feeding showed steady declines in the composite activity measure over the 24-week intervention period -- from about 2,900 units at baseline to 2,200 at week 24.

The cohort assigned to caloric restriction showed an initial decline but it was followed at week 12 with a countervailing increase. At week 24, the mean activity level was virtually identical to that at baseline.

Salvatore said the differing pattern of results between the baseline high- versus low-activity groups was something of a surprise. In the "Bruce Jenners," results at 6 weeks showed sharp drops in activity for both diet interventions. However, in those feeding freely, the drop continued to week 18 before leveling off at about 25% below baseline. Rats on the low-cal diet, in contrast, showed increases in activity back nearly to baseline where it remained.

In the baseline "couch potatoes," activity levels on the low-cal diet increased steadily to week 18 but then dropped at week 24, perhaps reflecting the limits of what the diet could accomplish. The sedentary rats allowed unlimited feeding showed progressive declines through week 24.

Arnold's exercise study indicated that 12 days of consecutive treadmill exercise had powerful short-term effects on spontaneous activity. At the end of the first cycle, activity measurements in the exercised rats averaged about 4,700 units, compared with 4,000 for controls. Two weeks later, though, the effect had dissipated, with activity levels in both groups dipping to about 3,500 units.

But the initial exercise regimen appeared to make the rats more responsive to additional cycles of exercise. After a month of inactivity, both of the initial groups were put on 12 days of treadmill exercise. The increase from pre-exercise baseline was greater in the rats who had the first cycle of exercise (about 240% versus 180% in the initially unexercised rats, P<0.05).

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